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WO2019195396A1 - Dispositifs et systèmes de fractionnement de particules d'encapsulation et leurs procédés d'utilisation - Google Patents

Dispositifs et systèmes de fractionnement de particules d'encapsulation et leurs procédés d'utilisation Download PDF

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Publication number
WO2019195396A1
WO2019195396A1 PCT/US2019/025551 US2019025551W WO2019195396A1 WO 2019195396 A1 WO2019195396 A1 WO 2019195396A1 US 2019025551 W US2019025551 W US 2019025551W WO 2019195396 A1 WO2019195396 A1 WO 2019195396A1
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Prior art keywords
block copolymer
liquid
copolymer material
mesoporous
mesoporous isoporous
Prior art date
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Ceased
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PCT/US2019/025551
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English (en)
Inventor
Rachel M. Dorin
Spencer W. ROBBINS
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Terapore Technologies Inc
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Terapore Technologies Inc
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Publication date
Application filed by Terapore Technologies Inc filed Critical Terapore Technologies Inc
Priority to SG11202009658WA priority Critical patent/SG11202009658WA/en
Priority to JP2020554107A priority patent/JP7495353B2/ja
Priority to US17/045,105 priority patent/US20210146316A1/en
Priority to CA3095610A priority patent/CA3095610A1/fr
Priority to EP19781335.5A priority patent/EP3774003A4/fr
Priority to MX2020010445A priority patent/MX2020010445A/es
Priority to CN201980030513.8A priority patent/CN112074339A/zh
Priority to KR1020207031702A priority patent/KR20200140330A/ko
Publication of WO2019195396A1 publication Critical patent/WO2019195396A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D61/00—Processes of separation using semi-permeable membranes, e.g. dialysis, osmosis or ultrafiltration; Apparatus, accessories or auxiliary operations specially adapted therefor
    • B01D61/14—Ultrafiltration; Microfiltration
    • B01D61/145—Ultrafiltration
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D69/00—Semi-permeable membranes for separation processes or apparatus characterised by their form, structure or properties; Manufacturing processes specially adapted therefor
    • B01D69/02—Semi-permeable membranes for separation processes or apparatus characterised by their form, structure or properties; Manufacturing processes specially adapted therefor characterised by their properties
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D71/00—Semi-permeable membranes for separation processes or apparatus characterised by the material; Manufacturing processes specially adapted therefor
    • B01D71/06—Organic material
    • B01D71/26—Polyalkenes
    • B01D71/261—Polyethylene
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D71/00—Semi-permeable membranes for separation processes or apparatus characterised by the material; Manufacturing processes specially adapted therefor
    • B01D71/06—Organic material
    • B01D71/28—Polymers of vinyl aromatic compounds
    • B01D71/281—Polystyrene
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D71/00—Semi-permeable membranes for separation processes or apparatus characterised by the material; Manufacturing processes specially adapted therefor
    • B01D71/06—Organic material
    • B01D71/28—Polymers of vinyl aromatic compounds
    • B01D71/282—Polyvinylphenol
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D71/00—Semi-permeable membranes for separation processes or apparatus characterised by the material; Manufacturing processes specially adapted therefor
    • B01D71/06—Organic material
    • B01D71/28—Polymers of vinyl aromatic compounds
    • B01D71/283—Polyvinylpyridine
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D71/00—Semi-permeable membranes for separation processes or apparatus characterised by the material; Manufacturing processes specially adapted therefor
    • B01D71/06—Organic material
    • B01D71/76—Macromolecular material not specifically provided for in a single one of groups B01D71/08 - B01D71/74
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D71/00—Semi-permeable membranes for separation processes or apparatus characterised by the material; Manufacturing processes specially adapted therefor
    • B01D71/06—Organic material
    • B01D71/76—Macromolecular material not specifically provided for in a single one of groups B01D71/08 - B01D71/74
    • B01D71/80—Block polymers
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
    • C08J5/00—Manufacture of articles or shaped materials containing macromolecular substances
    • C08J5/18—Manufacture of films or sheets
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D2325/00—Details relating to properties of membranes
    • B01D2325/02—Details relating to pores or porosity of the membranes
    • B01D2325/021—Pore shapes
    • B01D2325/0212—Symmetric or isoporous membranes
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D2325/00—Details relating to properties of membranes
    • B01D2325/02—Details relating to pores or porosity of the membranes
    • B01D2325/022—Asymmetric membranes
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D2325/00—Details relating to properties of membranes
    • B01D2325/02—Details relating to pores or porosity of the membranes
    • B01D2325/0283—Pore size
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
    • C08J2323/00—Characterised by the use of homopolymers or copolymers of unsaturated aliphatic hydrocarbons having only one carbon-to-carbon double bond; Derivatives of such polymers
    • C08J2323/02—Characterised by the use of homopolymers or copolymers of unsaturated aliphatic hydrocarbons having only one carbon-to-carbon double bond; Derivatives of such polymers not modified by chemical after treatment
    • C08J2323/04—Homopolymers or copolymers of ethene
    • C08J2323/08—Copolymers of ethene
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
    • C08J2325/00—Characterised by the use of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by an aromatic carbocyclic ring; Derivatives of such polymers
    • C08J2325/02—Homopolymers or copolymers of hydrocarbons
    • C08J2325/04—Homopolymers or copolymers of styrene
    • C08J2325/06—Polystyrene
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
    • C08J2339/00—Characterised by the use of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by a single or double bond to nitrogen or by a heterocyclic ring containing nitrogen; Derivatives of such polymers
    • C08J2339/04—Homopolymers or copolymers of monomers containing heterocyclic rings having nitrogen as ring member
    • C08J2339/08—Homopolymers or copolymers of vinyl-pyridine
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
    • C08J2423/00—Characterised by the use of homopolymers or copolymers of unsaturated aliphatic hydrocarbons having only one carbon-to-carbon double bond; Derivatives of such polymers
    • C08J2423/02—Characterised by the use of homopolymers or copolymers of unsaturated aliphatic hydrocarbons having only one carbon-to-carbon double bond; Derivatives of such polymers not modified by chemical after treatment
    • C08J2423/04—Homopolymers or copolymers of ethene
    • C08J2423/08—Copolymers of ethene
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
    • C08J2425/00—Characterised by the use of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by an aromatic carbocyclic ring; Derivatives of such polymers
    • C08J2425/02—Homopolymers or copolymers of hydrocarbons
    • C08J2425/04—Homopolymers or copolymers of styrene
    • C08J2425/06—Polystyrene
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
    • C08J2439/00—Characterised by the use of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by a single or double bond to nitrogen or by a heterocyclic ring containing nitrogen; Derivatives of such polymers
    • C08J2439/04—Homopolymers or copolymers of monomers containing heterocyclic rings having nitrogen as ring member
    • C08J2439/08—Homopolymers or copolymers of vinyl-pyridine

Definitions

  • the disclosure relates to methods of using mesoporous isoporous block copolymer materials for the fractionation of liquids comprising encapsulating particles.
  • the disclosure also relates to devices comprising mesoporous isoporous block copolymer materials for the fractionation of liquids comprising encapsulating particles
  • Encapsulating particles include, without limitation, structures such as cells, viruses, vesicles, liposomes, vacuoles, lysosomes, exosornes, and polymersomes. More generally these encapsulating particles comprise an outer barrier which encapsulates its interior contents, which can comprise gases, liquids, or solids, or any combination of gases, liquids or solids. Separating encapsulating particles from liquids is especially challenging since the particles are generally susceptible to rupture, deformation, and caking.
  • One common strategy for separating encapsulating particles is filtration using a filter/membrane. When selecting a filter for such a separation, the membrane/filter pore size should be small enough to exclude the encapsulating particle, but large enough to prevent clogging and low volumetric flux.
  • Blood fractionation is a common example of separating encapsulating particles, wherein blood cells are separated from the blood plasma. Blood fractionation is used for various applications, including clinical blood analysis and the isolation of blood plasma proteins for patient care and pharmaceutical production. Separating the blood cells from the plasma is typical for many applications.
  • a common technique for blood fractionation, especially in clinical analysis, is centrifugation. Centrifugation requires a centrifuge, which is not practical in every environment. For example, in an automated blood analysis machine, the inclusion of a centrifuge introduces an additional component requiring maintenance and adds to cost and bulk. Centrifuges are also inconvenient in point-of-care use.
  • Red blood cells have a maximum diameter of about 8 pm but can deform under pressure and pass through pores about 3 pm When filtering whole blood with pores of about 3 pm, the red blood cells deform and become stuck in the pores, which is called pore plugging. Pore plugging causes lower flow and if pressure is increased to raise flow, the cells lyse, expelling their contents, which is undesirable. To mitigate pore plugging, smaller pores can he used, generally in the range of about 800 nm to about 2 pm. However, it is also known that decreasing the pore size causes the red blood cells to cake on the membrane surface, causing lowered flux or even complete volumetric flux loss.
  • Brail et al. Transfusion Medicine Reviews, Vol IX, No. 2, 1995 pp 145-166
  • Kitagawa et al both indicate that a pore size (Brail) or average hydraulic diameter (Kitagawa) which is effectively a pore size, of 3 pm allows red blood cells through the membrane.
  • Togawa et al. (US Patent # 7927810 B2) indicates that red blood cells might even pass through 2 pm pores.
  • Kitagawa et al. indicates a lower useful hydraulic diameter of 500 nm, because blood clogs the filter below 500 nm and further causes lysis if the pressure is raised.
  • Block copolymer membranes have many broadly useful properties for filtration including: narrow pore size distributions, high pore densities, and tunable pore sizes in the 1 nm to 200 nm range.
  • Related art teaches that the smaller pore sizes and higher pore densities associated with block copolymer membranes would worsen the filtration of encapsulating particles such as blood cells in whole blood.
  • the materials and devices of this disclosure enable blood filtration under pressure without the expected lysis of ceils. To anyone skilled in the art, this improvement is beneficial for broad range of fractionation of liquid comprising encapsulated particles.
  • Fig. 1 is an illustration of an example of a mesoporous isoporous block copolymer material.
  • FIG. 2 is a schematic of an embodiment in accordance with various aspects of the present disclosure, wherein a liquid comprising encapsulating particles is fractionated by contact with a mesoporous isoporous block copolymer material.
  • FIG. 3 is a schematic of another embodiment in accordance with various aspects of the present disclosure, wherein a liquid comprising encapsulating particles is fractionated by contact with a mesoporous isoporous block copolymer material wherein the liquid is pressurized.
  • FIG. 4 is a schematic of yet another embodiment in accordance with various aspects of the present disclosure, wherein a liquid comprising encapsulating particles is fractionated by contact with a mesoporous isoporous block copolymer material wherein vacuum is applied to the mesoporous isoporous block copolymer material.
  • FIG. 5 is a schematic of yet another embodiment in accordance with various aspects of the present disclosure, wherein a liquid comprising encapsulating particles is fractionated once by contact with a mesoporous i soporous block copolymer material, then said fractionated liquid is fractionated a second time by contact with a second mesoporous isoporous block copolymer material.
  • FIG. 6 is a schematic of yet another embodiment in accordance with various aspects of the present disclosure, wherein a liquid comprising encapsulating particles is fractionated once by contact with a mesoporous isoporous block copolymer material wherein the liquid is pressurized, then said fractionated liquid is fractionated a second time by contact with a second mesoporous isoporous block copolymer material.
  • Fig. 7 is a schematic of yet another embodiment in accordance with various aspects of the present disclosure, wherein a liquid comprising encapsulating particles is fractionated once by contact with a mesoporous isoporous block copolymer material, then said fractionated liquid is fractionated a second time by contact with a second mesoporous isoporous block copolymer material wherein vacuum is applied at or near the outlet of the second mesoporous isoporous block copolymer material providing a pressure differential across both membranes.
  • Fig. 8 is a schematic of yet another embodiment in accordance with various aspects of the present disclosure, wherein a liquid comprising encapsulating particles is fractionated once by contact with a mesoporous isoporous block copolymer material in crossflow mode, then the permeate is fractionated a second time by contact with a second mesoporous isoporous block copolymer material in crossflow mode.
  • Fig. 9 is a schematic of yet another embodiment in accordance with various aspects of the present disclosure, wherein a liquid comprising encapsulating particles is fractionated once by contact with a mesoporous isoporous block copolymer material in crossflow mode, then the retentate is fractionated by contact with a second mesoporous isoporous block copolymer material in crossflow 7 mode.
  • FIG. 10 is an illustration of an exemplary 7 device in accordance with various aspects of the present disclosure.
  • FIG. 11 is an illustration of another exemplary device in accordance with various aspects of the present disclosure.
  • Fig. 12 is an illustration of yet another exemplary device in accordance with various aspects of the present disclosure.
  • FIG. 13 is an illustration of yet another exemplary device in accordance with various aspects of the present disclosure.
  • FIG. 14 is an illustration of yet another exemplary device in accordance with various aspects of the present disclosure.
  • FIG. 15 is an illustration of yet another exemplary device in accordance with various aspects of the present disclosure.
  • FIG. 16 is an illustration of yet another exemplary' device in accordance with various aspects of the present disclosure.
  • FIG. 17 is an illustration of yet another exemplary device in accordance with various aspects of the present disclosure.
  • FIG. 18 is an illustration of yet another exemplary device in accordance with various aspects of the present disclosure.
  • FIG. 19 is an illustration of yet another exemplary device in accordance with various aspects of the present disclosure.
  • Fig. 20 is UV-Visible spectra of a diluted whole blood solution (A, dashed) and a diluted permeate after filtration through a mesoporous isoporous block copolymer material (B, solid black).
  • Fig. 21 is optical microscopy images of whole blood showing blood cells (A, left), compared with permeate notably absent of color or blood cells after filtration through a mesoporous isoporous block copolymer material (B, right).
  • ranges are used as shorthand for describing each and every value that is within the range. Any value within the range can be selected as the terminus of the range.
  • the terms“comprise” (as well as forms, derivatives, or variations thereof, such as “comprising” and“comprises”),“include” (as well as forms, derivatives, or variations thereof, such as“including” and“includes”) and“has” (as well as forms, derivatives, or variations thereof, such as“having” and“have”) are inclusive (i.e , open-ended) and do not exclude additional elements or steps. Accordingly, these terms are intended to not only cover the recited element(s) or step(s), but may also include other elements or steps not expressly recited.
  • the present disclosure relates to a device comprising at least one mesoporous isoporous block copolymer material for fractionating a liquid comprising encapsulating particles.
  • the present disclosure also relates to a method for fractionating a liquid comprising encapsulating particles using at least one mesoporous isoporous block copolymer material.
  • “isoporous” means having a substantially narrow pore diameter distribution.
  • “mesoporous” means having pore diameters of about 1 to about 200 nanometers.
  • an“encapsulating particle” means a particle comprising an outer barrier which encapsulates its interior contents; the interior contents can comprise gases, liquids, or solids, or any combination of gases, liquids or solids.
  • a“selective portion” of a mesoporous isoporous block copolymer material can be defined as a portion of material comprising porosity.
  • the“most selective portion” of a mesoporous isoporous block copolymer material can be defined as a selective portion of the material comprising the smallest average pore diameter.
  • the“least selective portion” of a mesoporous isoporous block copolymer material can be defined as a selective portion of the material comprising the largest average pore diameter.
  • “retentate” means the liquid that does not pass through the porous material.
  • a raesoporous isoporous block copolymer material can have mesopores with diameters ranging from about 1 nm to about 200 nm. In some instances, the mesopores can range from about 3 nm to about 200 nm in diameter. In other instances, the mesopores can range from about 5 nm to about 200 nm in diameter. In yet other instances, the mesopores can range from about 5 nm to about 100 nm in diameter.
  • the mesopores can range from about 10 nm to about 100 nm in diameter. In yet other instances, the mesopores can range from about 5 nm to about 49 nm in diameter. In yet other instances, the mesopores can range from about 20 nm to about 49 nm in diameter. In yet other instances, the mesopores can range from about 1 nm to about 49 nm in diameter. In yet other instances, the mesopores can range from about 5 nm to about 50 nm in diameter. In yet other instances, the mesopores can range from about 5 nm to about 15 nm in diameter.
  • Block copolymer membranes have many useful properties for filtration including narrow pore size distributions (isoporosity), high pore densities, and tunable pore sizes in the about 1 nm to about 200 nm range.
  • the most selective layer of at least one mesoporous isoporous block copolymer material faces the incoming liquid comprising encapsulating particles and the most selective layer’s average pore diameters are significantly smaller than the maximum diameter of at least one of the encapsulating particles.
  • l is at least 100. In other instances, l is at least about 150. In yet other instances, l is at least about 200. In yet other instances, l is at least about 300. In yet other instances, l is at least about 350. In yet other instances., l is at least about 375. In yet other instances, l is at least about 400. In yet other instances, l is at least about 500. In yet other instances, l is at least about 600. In yet other instances, l is at least about 700. In yet other instances, l is at least about 800. In yet other instances, l is at least about 850. In yet other instances, l is at least about 900.
  • l is at least about 1000 In yet other instances, l is at least about 1500. In yet other instances, l is at least about 15000. In some embodiments, l is at most 30,000. In an instance, l is at most 25,000. In another instance, l is at most 20,000. In yet another instance, k is at most 18,000 Examples in accordance with the present disclosure are found in Table 1.
  • the mesoporous isoporous block copolymer material is a two-dimensional (e.g. sheet, film) or three-dimensional structure (e.g. tube, monolith) and comprises material comprising block copolymer 20, and mesopores 10.
  • the mesoporous isoporous block copolymer material can be asymmetric or symmetric in cross- sectional structure.
  • a symmetric membrane is one with pore structure that is uniform through its thickness while an asymmetric membrane is one with a pore structure that varies through the thickness.
  • At least one mesoporous isoporous block copolymer material 200 is contacted with a liquid comprising encapsulating particles 210, causing at least one component of the liquid to be separated or removed, and a permeate 220, is collected as a once fractionated liquid 230.
  • At least one mesoporous isoporous block copolymer material 300 is contacted with a liquid comprising encapsulating particles 310 and a pressure differential is applied across the mesoporous isoporous block copolymer material 300 using a pressurization source 320, causing at least one component of the liquid to be separated or removed, and a permeate 330 is collected as a once fractionated liquid 50.
  • At least one mesoporous isoporous block copolymer material 400 is contacted with a liquid comprising encapsulating particles 410 and a pressure differential is applied across the mesoporous isoporous block copolymer material 400 using a vacuum source 420, causing at least one component of the liquid to be separated or removed, and a permeate 430 is collected as a once fractionated liquid 440.
  • At least one mesoporous isoporous block copolymer material is contacted with a liquid comprising encapsulating particles, and a variable or intermittent pressure differential is applied across the mesoporous isoporous block copolymer material, causing at least one component of the liquid to be separated or removed
  • a variable or intermittent pressure differential can serve to disrupt any buildup at the surface.
  • At least one mesoporous isoporous block copolymer material wherein the cross-sectional structure of the mesoporous isoporous block copolymer material is symmetric, is contacted with a liquid comprising encapsulating particles, causing at least one component of the liquid to be separated or removed
  • At least one mesoporous isoporous block copolymer material wherein the cross-sectional structure of the mesoporous isoporous block copolymer material is asymmetric, is contacted with a liquid comprising encapsulating particles, causing at least one component of the liquid to be separated or removed.
  • At least one mesoporous i soporous block copolymer material is contacted with a liquid comprising encapsulating particles, wherein the liquid contacts the most selective portion of the mesoporous isoporous block copolymer material first, causing at least one component of the liquid to be separated or removed.
  • a device in accordance with various aspects of the present disclosure comprises at least one mesoporous isoporous block copolymer material.
  • a device in accordance with various aspects of the present disclosure comprises at least one mesoporous isoporous block copolymer material, an inlet to allow said liquid to contact said mesoporous isoporous block copolymer material, and an outlet to allow passage of the fractionated liquid.
  • a device in accordance with various aspects of the present disclosure comprises at least one mesoporous isoporous block copolymer material, an inlet to allow ? said liquid to contact said mesoporous isoporous block copolymer material, an outlet to allow passage of the fractionated liquid, and a vent to remove gas from the device.
  • a device in accordance with various aspects of the present disclosure comprises at least one mesoporous isoporous block copolymer material, an inlet to allow said liquid to contact said mesoporous isoporous block copolymer material, an outlet to allow passage of the fractionated liquid, and a retentate outlet to remove unfiltered liquid.
  • a device in accordance with various aspects of the present disclosure comprises at least one mesoporous isoporous block copolymer material, an inlet to allow said liquid to contact said mesoporous isoporous block copolymer material, an outlet to allow passage of the fractionated liquid, and a receiving vessel to capture fractionated liquid.
  • a device in accordance with various aspects of the present disclosure comprises at least one mesoporous isoporous block copolymer material, an inlet to allow said liquid to contact said mesoporous isoporous block copolymer material, an outlet to allow passage of the fractionated liquid and at least two of the following: a vent to remove gas from the device, a retentate outlet to remove unfiltered liquid, and a receiving vessel to capture fractionated liquid.
  • a device in accordance with various aspects of the present disclosure comprises at least one mesoporous isoporous block copolymer material, an inlet to allow said liquid to contact said mesoporous isoporous block copolymer material, an outlet to allow passage of the fractionated liquid, a vent to remove gas from the device, a retentate outlet to remove unfiltered liquid, and a receiving vessel to capture fractionated liquid.
  • a device in accordance with various aspects of the present disclosure comprises at least one mesoporous isoporous block copolymer material comprising an asymmetric cross-section wherein the most selective mesoporous portion of at least the first mesoporous isoporous block copolymer material faces the inlet such that any incoming liquid contacts the most selective portion of said mesoporous isoporous material first.
  • a device in accordance with various aspects of the present disclosure comprises an inlet and the inlet can be part of a housing for a mesoporous isoporous block copolymer material.
  • the inlet can be a molded plastic part of a syringe filter.
  • the inlet can simply be the exposed surface of a mesoporous isoporous block copolymer material wherein liquid can be introduced to contact a mesoporous isoporous block copolymer material.
  • the inlet can be the most selective portion of a mesoporous isoporous block copolymer material wherein the mesoporous isoporous block copolymer material is a flat sheet membrane.
  • a device in accordance with various aspects of the present disclosure comprises an outlet and the outlet can be part of a housing for a mesoporous isoporous block copolymer material.
  • the outlet can be a plastic part of a hollow fiber module.
  • the outlet can simply be the exposed surface of a mesoporous isoporous block copolymer material wherein liquid can exit a mesoporous isoporous block copolymer material.
  • the outlet can be the least selective portion of a mesoporous isoporous block copolymer material wherein the mesoporous isoporous block copolymer material is a flat sheet membrane attached to the bottom of a multiple well plate.
  • a device in accordance with various aspects of the present disclosure comprises a vent for removing gas from the device as or after a liquid is introduced.
  • the vent can be an opening that can be opened or closed.
  • the vent is a valve incorporated into a housing that can be manually or remotely actuated to transition between an open state, partially open state, or closed state.
  • the vent is a molded part of a housing that has a removable cap, cover, or fitting allowing for opening, partial opening, and closing.
  • the vent is an opening or connection where an external valve, fitting, connector, cover, or cap can be connected, and used to meter the vent between an open state and a closed state.
  • a device in accordance with various aspects of the present disclosure comprises a receiving vessel to capture fractionated liquid.
  • the receiving vessel is an integrated portion of the device.
  • the receiving vessel is a removable portion of the device.
  • At least one mesoporous isoporous block copolymer material is contacted with a liquid comprising encapsulating particles, wherein the liquid contacts the most selective portion of the mesoporous isoporous block copolymer material first and a pressure differential is applied across the mesoporous isoporous block copolymer material, causing at least one component of the liquid to be separated or removed.
  • Pressurization can be applied, for example, by manual or mechanical actuation of a plunger as found, for example, on a syringe. Pressurization can also be applied, for example, by a gas or a liquid driven from a pump or a pressurized container of said gas or liquid.
  • At least one mesoporous isoporous block copolymer material is contacted with a liquid comprising encapsulating particles, wherein at least one component is separated or removed, with or without a pressure differential applied across the mesoporous isoporous block copolymer material, while minimizing lysis of the encapsulating particles.
  • encapsulating particle lysis is less than about 1% of particles lysed. In another instance, encapsulating particle lysis is less than about 5% of particles lysed. In yet another instance, encapsulating particle lysis is less than about 10% of particles lysed.
  • Vacuum can be applied, for example, by drawing down a plunger manually or mechanically on, for example, a syringe. Vacuum can also be applied, for example, from a vacuum pump. In some embodiments, the vacuum is applied directly from the device outlet. For example, a syringe can be connected to the device outlet and drawn back to apply vacuum. In some instances, a splitter can be included on the outlet to allow for vacuum application on one port and liquid collection through another port.
  • a vacuum filtration device wherein the vacuum connection is above the device outlet, encapsulated by a receiving vessel. In this example, vacuum aids the fractionation, but since the outlet is below the vacuum source, the fractionated liquid can be collected without being sucked directly into the vacuum source.
  • At least one mesoporous isoporous block copolymer material is contacted with whole blood, wherein at least one component of the whole blood is separated or removed.
  • At least one mesoporous isoporous block copolymer material is contacted with a liquid comprising whole blood, wherein at least one component of the whole blood is separated or removed.
  • At least one mesoporous isoporous block copolymer material is contacted with a liquid comprising at least one type of blood cell, wherein the at least one type of blood cell is separated or removed.
  • At least one mesoporous isoporous block copolymer material is contacted with a liquid comprising blood and further comprising at least one preservative including but not limited to EDTA, an oxalate salt, sodium citrate, sodium iodoacetate, sodiu fluoride, and heparin, causing at least one component of the blood to be separated or removed.
  • a liquid comprising blood and further comprising at least one preservative including but not limited to EDTA, an oxalate salt, sodium citrate, sodium iodoacetate, sodiu fluoride, and heparin
  • At least one mesoporous isoporous block copolymer material is imbibed with at least one preservative including but not limited to EDTA, an oxalate salt, sodium citrate, sodium iodoacetate, sodium fluoride, and heparin.
  • the mesoporous isoporous block copolymer material is packaged as or in a device including, for example: a pleated pack, one or more flat sheets in a cassette, a spiral wound module, hollow fibers, a hollow fiber module, a. syringe filter, a microcentrifuge tube, a. centrifuge tube, a spin column, a multiple well plate, a vacuum filter, or a pipette tip.
  • a device can utilize more than one different material of the disclosure.
  • At least one component that is separated or removed from the liquid comprising encapsulating particles is collected or recovered after contacting the mesoporous i soporous block copolymer.
  • more than one mesoporous isoporous block copolymer material or device comprising mesoporous isoporous material is used during the fractionation of the liquid comprising one or more sizes of encapsulating particles.
  • a liquid comprising encapsulating particles 500 is contacted with a mesoporous isoporous block copolymer material 510, and a permeate 520 is collected as a once fractionated liquid 530.
  • the once fractionated liquid 530 is subsequently contacted with a second mesoporous isoporous material 540, and a permeate 550 is collected as a twice fractionated liquid 560.
  • a liquid comprising encapsulating particles 600 is contacted with a mesoporous isoporous block copolymer material 610 and pressurized using a pressurization source 620, and a first permeate 630 is collected as a once fractionated liquid 640.
  • the once fractionated liquid 640 is subsequently contacted with a second mesoporous isoporous material 650, and a second permeate 660 is collected as a twice fractionated liquid 670.
  • a liquid comprising encapsulating particles 700 is contacted with a mesoporous isoporous block copolymer material 710, and a first permeate 720 is collected as a once fractionated liquid 730.
  • the once fractionated liquid 730 is subsequently contacted with a second mesoporous isoporous material 740, and vacuum is applied across the membrane using a vacuum source 760.
  • a second permeate 770 is collected as a twice fractionated liquid 780.
  • a syringe filter device comprising mesoporous isoporous block copolymer material is contacted with a liquid comprising encapsulating particles and a pressure gradient is applied across the syringe filter device, facilitating the separation of larger particles.
  • the permeate is contacted with a surface functionalized monolithic mesoporous i soporous block copolymer material packaged in a pipette tip and a pressure differential is applied across the mesoporous isoporous block copolymer material, facilitating the separation of some of the smaller particles.
  • the retained blood proteins can be recovered from the mesoporous isoporous block copolymer material.
  • At least one mesoporous isoporous block copolymer material or device comprising mesoporous isoporous block copolymer material is operated in crossflow or tangential flow mode, wherein the liquid comprising encapsulating particles is passed tangential to the mesoporous isoporous selective portion of the material.
  • more than one mesoporous isoporous block copolymer material or device comprising mesoporous isoporous block copolymer material is used for the separation of the liquid comprising encapsulating materials.
  • a liquid comprising encapsulating particles 800 is first separated by contacting a first mesoporous isoporous block copolymer material 810 in crossflow mode, where a first retentate 820 is cycled back into a first feed 830 and a first permeate 840 from the first separation is collected as a once fractionated liquid 850.
  • the once fractionated liquid 850 is then contacted with a second mesoporous isoporous block copolymer material 860 in crossflow mode, where a second retentate 870 is cycled back into a second feed 880 and a second permeate 890 from the second separation is collected as a twice fractionated liquid 895.
  • a liquid comprising encapsulating particles 900 is first separated by contacting a first mesoporous isoporous block copolymer material 910 in crossflow mode, where a first retentate 920 is further separated by a second mesoporous isoporous block copolymer material 930 in crossflow mode where a second retentate 940 can optionally be cycled back into a feed of the first retentate 920.
  • a first permeate 950 obtained from the first separation using the first mesoporous isoporous block copolymer material 910, is collected as a once fractionated liquid 960.
  • a liquid comprising encapsulating particles is first separated by a mesoporous i soporous block copolymer material in crossflow mode, and secondly, the retentate from the first separation is then contacted with a second mesoporous isoporous block copolymer material in crossflow mode for further separation.
  • At least one mesoporous isoporous block copolymer material comprises a diblock copolymer.
  • At least one mesoporous isoporous block copolymer material compri ses a triblock copolymer.
  • at least one mesoporous isoporous block copolymer material comprises an A-B-A triblock copolymer.
  • at least one mesoporous isoporous block copolymer material comprises an A-B-C triblock copolymer. Any block architecture, so long as the material is mesoporous and isoporous and comprises at least one block copolymer, is suitable.
  • At least one mesoporous isoporous block copolymer material comprises a tetrablock or higher order copolymer, e.g. pentablock, heptablock, etc.
  • Any block architecture, so long as the material is mesoporous and isoporous and comprises at least one block copolymer is suitable, for example, A-B-A-B, A-B-C-A, A-B-C-B, A-B-C-D, A-B-C-D-E, A-B ⁇ A-C-D-E, A-B-A-B-A-B-A, A-B-C-A-B-A-C-D, etc,
  • block chemistries include, but are not limited to: Poly(isobutylene), Poly(isoprene), Polyfbutadiene), Polypropylene glycol), Poly(ethylene oxide), Poly(dimethylsiloxane), Poiy(ethersuifone), Poly (sul tone), Poly(hydroxystyrene),
  • suitable mesoporous i soporous block copolymer materials include those with Mn of about 1 x 10 J to about 1 x 10 ' g/mol and include diblock, triblock, or multiblock copolymers of higher order (i .e., tetrablock, pentablock, etc ).
  • Polydispersity index (PD!) of a block copolymer is the measure of heterogeneity of the size of molecules and shows the distribution of molar mass in the block copolymer sample. It is the ratio of average molar mass (M w ) and number-average molar mass (Mn).
  • the PDI of at least one embodiment of a BCP disclosed herein is in the range of about 1.0 to about 3.0.
  • suitable mesoporous isoporous block copolymer materials comprise at least one diblock copolymer or multiblock copolymer, having a structure in the form of A-B, B- A, B-A-B, A-B -A-B, B-A-B-A, or A-B-A, wherein A and B represent two distinct types of block chemistries.
  • A is a hydrophilic and/or hydrogen-bonding block and B is a hydrophobic block.
  • Suitable hydrogen-bonding and/or hydrophilic blocks include, but are not limited to, po!yviny!pyridines, polyethylene oxides, polyacrylic acids, poly(hydroxystyrene), polyacrylates and polymethacrylates, substituted polyacrylates and polymethacrylates.
  • hydrophilic blocks include: poly(acrylic acid), poly(acrylamide), poly(vinylpyridine), poly(vinylpyrrolidone), poly(vinyl alcohol), naturally derived polymers such as cellulose and chitosan, poly(ether), poly(maleic anhydride), polyfN-isopropylacry!amide), poly(styrene sulfonate), poly(allyihydrochloride), poly(sulfone), poly(ethersulfone), poly(ethylene glycol), po!y(2-hydroxyethyl methacrylate).
  • hydrogen bonding blocks include: poly(vinylpyridine), poly(ethylene oxide), poly(methacrylate), poly(methyl methacrylate), poly(dimethylethyl amino ethyl methacrylate), poly(dimethylaminoethyl methacrylate) polyCacry!ic acid), poly(hydroxystyrene), poly(dimethylacryJamide).
  • Suitable hydrophobic blocks can include, but are not limited to, polystyrenes, e.g., polystyrene and poly(alkyl substituted styrene) such as poly (alpha-methyl styrene), polypropylenes, poly(vinyl chlorides), polybutadiene, poly(isoprene), poiyfethylene- ,s a -butylene), poly(ethylene-a//-propylene), and polytetrafluoroethylenes.
  • polystyrenes e.g., polystyrene and poly(alkyl substituted styrene) such as poly (alpha-methyl styrene), polypropylenes, poly(vinyl chlorides), polybutadiene, poly(isoprene), poiyfethylene- ,s a -butylene), poly(ethylene-a//-propylene), and polytetrafluoroethylenes.
  • At least one mesoporous isoporous block copolymer material comprises a complex architecture.
  • a“complex” block structure or polymer architecture signifies more than one monomer, chemistry, configuration, or structure in at least one block, or adjacent to blocks.
  • a combination of different block copolymer starting materials is another complex architecture of the disclosure.
  • Nonlimiting examples of complex architecture include: gradient blocks, mixtures of monomers in blocks, cyclic blocks or overall cyclic structures, branched blocks, dendritic structures, mixtures of block copolymers, etc. Any block architecture, complex or not, is suitable, so long as the material is mesoporous and isoporous and comprises at least one block copolymer.
  • a device in accordance with various aspects of the present disclosure can be, for example, a flat sheet 1000 having an inlet 1020, a block copolymer material 1040, and an outlet 190; a configuration of such a device can be as illustrated in Fig. 10.
  • a device in accordance with various aspects of the present disclosure can be, for example, a syringe filter 1100 having an inlet 1120, a block copolymer material 1140, an outlet 1 160, and a vent 1180, a configuration of such a device can be as illustrated in Fig. 1 1.
  • a device in accordance with various aspects of the present disclosure can be, for example, a crossflow module 1200 having an inlet 1220, a block copolymer material 1240, an outlet 1260, and a retentate port 1280; a configuration of such a device can be as illustrated in Fig. 12.
  • a device in accordance with various aspects of the present disclosure device can be, for example, a spin column 1300 having an inlet 1320, a block copolymer material 1340, an outlet 1360, and a receiving vessel 1380; a configuration of such a device can be as illustrated in Fig. 13.
  • a device in accordance with various aspects of the present disclosure can be, for example, and a pleated capsule 1400 having an inlet 1420, a block copolymer material 1440, an outlet 1460, and a vent 1480; a configuration of such a device can be as illustrated in Fig.
  • a device in accordance with various aspects of the present disclosure can be, for example, a spiral wound module 1500 having an inlet 1520, a block copolymer material 1540, and an outlet 1560, and a vent or retentate port 1580; a configuration of such a device can be as illustrated in Fig 15.
  • a device in accordance with various aspects of the present disclosure can be, for example, a hollow fiber module 1600 having an inlet 1620, a block copolymer material 1640, and an outlet 1660, a configuration of such a device can be as illustrated in Fig 16.
  • the device can be, for example, a pipette tip 1700 having an inlet 1720, a block copolymer material 1740, and an outlet 1780; a configuration of such a device can be as illustrated in Fig 17.
  • a device in accordance with various aspects of the present disclosure can be, for example, a multiple well plate 1800, having an inlet 1820, a block copolymer material 1840, an outlet 1860, and a receiving vessel 1880; a configuration of such a device can be as illustrated in Fig. 18
  • the device can be, for example, a crossflow module 1900 having an inlet 1920, a block copolymer material 1940, an outlet 1960, and a vent 1980 and retentate port 1990; a configuration of such a device can be as illustrated in Fig. 19.
  • mesoporous isoporous material comprising the block copolymer poIy(isoprene)-Wock-poly(styrene)-Wock-poly(4- viny!pyridine) is used to fractionate a liquid comprising blood.
  • the material is a disc of 0.7 cm 2 active area, of a film with an asymmetric cross-sectional structure.
  • the pores on the side of the disc with the most selective pores are about 20 nm in diameter and this is the most selective portion.
  • the side of the membrane in this example that is the most selective portion contacts the liquid comprising blood first.
  • the liquid is a 1 :6 dilution of whole blood in 10 mM PBS buffer.
  • Fig 20 shows the UV- Visible spectra of the diluted stock (Fig. 20A, dashed line) and diluted permeate (Fig 20B, solid line). Notable in the spectra is the near-complete removal of all absorbing species including red blood cells and their visibly absorbing compounds, as well as protein absorption at 280 nm, upon filtration by an isoporous mesoporous block copolymer material.
  • the maximum absorption of the residual visibly absorbing species (around 400 nm) in the permeate is less than 1 % of the absorption max relative to the diluted whole blood stock, and is attributed to a very small amount of red blood ceil lysis, causing release of the colored compounds.
  • the diluted whol e bl ood (Fig. 21 A, left) shows blood cells throughout the view', while the undiluted permeate (Fig. 2 IB, right) shows no red blood cells and appears colorless.
  • major hemolysis occurs, for example aggressively freezing blood, the liquid appears bright red under the light microscope, even if intact red blood cells are not observed, and the image is much darker than what is observed in Fig. 2 IB.

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Abstract

Un procédé de fractionnement d'un liquide comprend la mise en contact d'un liquide comprenant au moins un type de particule d'encapsulation avec au moins un matériau copolymère séquencé isoporeux mésoporeux, au moins un composant du liquide étant séparé. Un dispositif de fractionnement d'un liquide ayant des particules d'encapsulation comprend au moins un matériau copolymère séquencé isoporeux mésoporeux. Le dispositif peut en outre comprendre une entrée pour permettre au liquide de venir en contact avec le matériau copolymère séquencé isoporeux mésoporeux, et une sortie pour permettre le passage du liquide fractionné. Dans certains cas, le dispositif peut être une capsule plissée, une cassette de feuille plate, un module enroulé en spirale, un module de fibre creuse, un filtre à seringue, un tube de micro-centrifugeuse, un tube de centrifugeuse, une colonne de centrifugation, une plaque de puits multiple, un filtre à vide, une feuille plate ou une pointe de pipette.
PCT/US2019/025551 2018-04-04 2019-04-04 Dispositifs et systèmes de fractionnement de particules d'encapsulation et leurs procédés d'utilisation Ceased WO2019195396A1 (fr)

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US17/045,105 US20210146316A1 (en) 2018-04-04 2019-04-04 Encapsulating particle fractionation devices and systems and methods of their use
CA3095610A CA3095610A1 (fr) 2018-04-04 2019-04-04 Dispositifs et systemes de fractionnement de particules d'encapsulation et leurs procedes d'utilisation
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